Bromoform → 3-Bromo-6-fluoroquinoline

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-Fluoroindole (2.00 g, 14.8 mmol) and benzyltriethylammonium chloride (168.5 mg, 0.740 mmol) in toluene (3.00 mL) and bromoform (3.00 mL) at 40° C. was added a solution of sodium hydroxide (4.44 g, 111 mmol) in water (12.0 mL) in a dropwise manner. The reaction then stirred at 40° C. for 48 h. After cooling, the solvent was evaporated and the residue was diluted with methyl tert-butyl ether (100 mL) and water (100 mL). The aqueous layer was extracted with methyl tert-butyl ether. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give 2.00 g of crude material. Purification by silica gel flash chromatography (0-2% ethyl acetate in petroleum ether) provided 3-bromo-6-fluoroquinoline (503 mg, 15% yield) as a white solid. 1H NMR (400 MHz, CD3OD, 6): 8.87 (d, J=2.0 Hz, 1H), 8.27 (d, J=2.0 Hz, 1H), 8.08 (dd, J=9.2, 5.6 Hz, 1H), 7.52-7.41 (m, 1H), 7.35 (dd, J=8.8, 2.8 Hz, 1H). (M+1): 225.6.

Provenance & Evidence